Influenza in long‐term care facilities Lansbury, Louise E.; Brown, Caroline S.; Nguyen‐Van‐Tam, Jonathan S.
Influenza and other respiratory viruses,
September 2017, Letnik:
11, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Long‐term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be ...introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long‐term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.
We use direct method oxygen abundances in combination with strong optical emission lines, stellar masses (M
⋆), and star formation rates (SFRs) to recalibrate the N2, O3N2, and N2O2 oxygen abundance ...diagnostics. We stack spectra of ∼200 000 star-forming galaxies from the Sloan Digital Sky Survey in bins of M
⋆ and SFR offset from the star-forming main sequence (
$ {\Delta \log (SSFR)}$
) to measure the weak emission lines needed to apply the direct method. All three new calibrations are reliable to within ±0.10 dex from log (M
⋆/M⊙) ∼ 7.5–10.5 and up to at least 200 M⊙ yr−1 in SFR. The N2O2 diagnostic is the least subject to systematic biases. We apply the diagnostics to galaxies in the local Universe and investigate the M
⋆–Z–SFR relation. The N2 and O3N2 diagnostics suggest the SFR dependence of the M
⋆–Z–SFR relation varies with both M
⋆ and
${\Delta \log (SSFR)}$
, whereas the N2O2 diagnostic suggests a nearly constant dependence on SFR. We apply our calibrations to a sample of high-redshift galaxies from the literature, and find them to be metal-poor relative to local galaxies with similar M
⋆ and SFR. The calibrations do reproduce direct method abundances of the local analogues. We conclude that the M
⋆–Z–SFR relation evolves with redshift.
PURPOSEEducational podcasts are an increasingly popular platform for teaching and learning in health professions education. Yet it remains unclear why residents are drawn to podcasts for educational ...purposes, how they integrate podcasts into their broader learning experiences, and what challenges they face when using podcasts to learn.
METHODThe authors used a constructivist grounded theory approach to explore residents’ motivations and listening behaviors. They conducted 16 semistructured interviews with residents from 2 U.S. and 1 Canadian institution from March 2016 to August 2017. Interviews were recorded and transcribed. The transcripts were analyzed using constant comparison, and themes were identified iteratively, working toward an explanatory framework that illuminated relationships among themes.
RESULTSParticipants described podcasts as easy to use and engaging, enabling both broad exposure to content and targeted learning. They reported often listening to podcasts while doing other activities, being motivated by an ever-present desire to use their time productively; this practice led to challenges retaining and applying the content they learned from the podcasts to their clinical work. Listening to podcasts also fostered participants’ sense of connection to their peers, supervisors, and the larger professional community, yet it created tensions in their local relationships.
CONCLUSIONSDespite the challenges of distracted, contextually constrained listening and difficulties translating their learning into clinical practice, residents found podcasts to be an accessible and engaging learning platform that offered them broad exposure to core content and personalized learning, concurrently fostering their sense of connection to local and national professional communities.
Bilayer graphene has been a subject of intense study in recent years. The interlayer registry between the layers can have dramatic effects on the electronic properties: for example, in the presence ...of a perpendicular electric field, a band gap appears in the electronic spectrum of so-called Bernal-stacked graphene Oostinga JB, et al. (2007) Nature Materials 7:151–157. This band gap is intimately tied to a structural spontaneous symmetry breaking in bilayer graphene, where one of the graphene layers shifts by an atomic spacing with respect to the other. This shift can happen in multiple directions, resulting in multiple stacking domains with soliton-like structural boundaries between them. Theorists have recently proposed that novel electronic states exist at these boundaries Vaezi A, et al. (2013) arXiv:1301.1690; Zhang F, et al. (2013) arXiv:1301.4205, but very little is known about their structural properties. Here we use electron microscopy to measure with nanoscale and atomic resolution the widths, motion, and topological structure of soliton boundaries and related topological defects in bilayer graphene. We find that each soliton consists of an atomic-scale registry shift between the two graphene layers occurring over 6–11 nm. We infer the minimal energy barrier to interlayer translation and observe soliton motion during in situ heating above 1,000 °C. The abundance of these structures across a variety of samples, as well as their unusual properties, suggests that they will have substantial effects on the electronic and mechanical properties of bilayer graphene.
•X-ray structures are now available for more than 60 ligands and 20 GPCRs.•Structures reveal details of ligand biding that could not be predicted.•Structure-based drug design for GPCRs has been ...transformed by the new results.•Lipophilic sites and water molecules have key roles in ligand-binding properties.
X-ray structures of G protein-coupled receptors (GPCRs) have now been reported for more than 60 ligands and 20 receptors, including examples from GPCR classes A, B, C and F. The new structures show previously unobtainable details of interactions between GPCRs and ligands, including the roles of lipophilic regions and water molecules as key drivers of binding. In addition, the structures have revealed several surprising ligand-binding modes, including sites outside the orthosteric pocket. This new information is dramatically changing the way we approach GPCR drug discovery.
Next-generation sequencing technologies have been and continue to be deployed in clinical laboratories, enabling rapid transformations in genomic medicine. These technologies have reduced the cost of ...large-scale sequencing by several orders of magnitude, and continuous advances are being made. It is now feasible to analyze an individual’s near-complete exome or genome to assist in the diagnosis of a wide array of clinical scenarios. Next-generation sequencing technologies are also facilitating further advances in therapeutic decision making and disease prediction for at-risk patients. However, with rapid advances come additional challenges involving the clinical validation and use of these constantly evolving technologies and platforms in clinical laboratories. To assist clinical laboratories with the validation of next-generation sequencing methods and platforms, the ongoing monitoring of next-generation sequencing testing to ensure quality results, and the interpretation and reporting of variants found using these technologies, the American College of Medical Genetics and Genomics has developed the following professional standards and guidelines.
Genet Med15 9, 733–747.
Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To ...gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes.
Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create ...diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians.
A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis.
Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases, confirming the original Lung-GPA. For melanoma and renal cell cancer, prognostic factors were Karnofsky performance score and the number of brain metastases. For breast cancer, prognostic factors were tumor subtype, Karnofsky performance score, and age. For GI cancer, the only prognostic factor was the Karnofsky performance score. The median survival times by GPA score and diagnosis were determined.
Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases.
Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 ...human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID
of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237 ; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study's primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. All pre-specified primary and secondary objectives were met. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log
copies per milliliter (median, 95% confidence interval (8.41, 9.53)). Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2-4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs present even in asymptomatic infection. All infected individuals developed serum spike-specific IgG and neutralizing antibodies. Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70-80% of viable virus had been generated. Thus, with detailed characterization and safety analysis of this first SARS-CoV-2 human challenge study in young adults, viral kinetics over the course of primary infection with SARS-CoV-2 were established, with implications for public health recommendations and strategies to affect SARS-CoV-2 transmission. Future studies will identify the immune factors associated with protection in those participants who did not develop infection or symptoms and define the effect of prior immunity and viral variation on clinical outcome.
Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of subjects with ...CHP have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF).
To determine the common and unique molecular features of CHP and IPF.
Transcriptome analysis of lung samples from CHP (
= 82), IPF (
= 103), and unaffected controls (
= 103) was conducted. Differential gene expression was determined adjusting for sex, race, age, and smoking history and using false discovery rate to control for multiple comparisons.
When compared with controls, we identified 413 upregulated and 317 downregulated genes in CHP and 861 upregulated and 322 downregulated genes in IPF. Concordantly upregulated or downregulated genes in CHP and IPF were related to collagen catabolic processes and epithelial development, whereas genes specific to CHP (differentially expressed in CHP when compared with control and not differentially expressed in IPF) were related to chemokine-mediated signaling and immune responsiveness. Using weighted gene coexpression network analysis, we found that among subjects with CHP, genes involved in adaptive immunity or epithelial cell development were associated with improved or reduced lung function, respectively, and that MUC5B expression was associated with epithelial cell development. MUC5B expression was also associated with lung fibrosis and honeycombing.
Gene expression analysis of CHP and IPF identified signatures common to CHP and IPF, as well as genes uniquely expressed in CHP. Select modules of gene expression are characterized by distinct clinical and pathological features of CHP.
PDF
